Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Imidazopyridazine and imidazothiadiazole compounds

a technology of imidazopyridazine and imidazothiadiazole, which is applied in the direction of drug composition, cardiovascular disorder, organic chemistry, etc., can solve the problems of limited efficacy, increased risk of bleeding, and limitations of current anti-platelet therapy

Active Publication Date: 2019-02-26
UNIV DE MONTREAL
View PDF11 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Current anti-platelet therapies have limitations including increased risk of bleeding as well as partial efficacy (relative cardiovascular risk reduction in the 20 to 30% range).

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Imidazopyridazine and imidazothiadiazole compounds
  • Imidazopyridazine and imidazothiadiazole compounds
  • Imidazopyridazine and imidazothiadiazole compounds

Examples

Experimental program
Comparison scheme
Effect test

example 1

N-(3-(((6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)benzofuran-4-yl)oxy)methyl)phenyl)benzamide

[0494]

[0495]A mixture of 6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)benzofuran-4-ol (0.050 g, 0.157 mmol, see WO13163279, WO13163241, and WO13163244 for preparation of this compound and related intermediates where R3 and Y in Formula I are modified), triphenylphosphine (0.083 g, 0.316 mmol) and N-(3-(hydroxymethyl)phenyl)benzamide (0.072 g, 0.316 mmol) (J. L. Kelly and B. R. Baker, J. Med. Chem., 1982, 25, 600) in a 50 ml flask was maintained under vacuum for 10 min and then purged with nitrogen. Dry tetrahydrofuran (4 ml) was added and the resulting heterogeneous mixture was treated at 22° C. with a solution of diisopropyl azodicarboxylate (0.064 g, 0.316 mmol) in tetrahydrofuran (2 ml) added drop-wise over 10 min. The resulting homogeneous solution was then stirred at 22° C. for 3 h. The reaction mixture was quenched by the addition of dichloromethane and s...

example 2

4-Fluoro-N-(3-(((6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)benzofuran-4-yl)oxy)methyl)phenyl)benzamide

[0496]

[0497]Reaction of 6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)benzofuran-4-ol (0.080 g, 0.252 mmol) with 4-fluoro-N-(3-(hydroxymethyl)phenyl)benzamide (0.092 g, 0.378 mmol) as described in example 1 gave 0.099 g (72% yield) of the title material as a white solid. HPLC (Method A): 2.371 min. HRMS (ESI) calcd for C28H22FN4O5S [M+H]+ m / z 545.1289, found 545.1301. 1H NMR (CDCl3, 400 MHz) δ ppm: 7.89-7.92 (m, 3H), 7.82 (s, 1H), 7.76 (br.d, J=7.9 Hz, 1H), 7.61 (s, 1H), 7.39 (t, J=7.9 Hz, 1H), 7.23 (overlapping with CHCl3, 1H), 7.15 (t, J=8.5 Hz, 2H), 7.09 (s, 1H), 6.67 (br. d, 1H), 6.36 (d, J=1.7 Hz, 1H), 5.18 (s, 2H), 4.19 (s, 3H), 3.82 (s, 3H).

[0498]

example 3

tert-Butyl (3-(((6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)benzofuran-4-yl)oxy)methyl)phenyl)carbamate

[0499]

tert-Butyl (3-(hydroxymethyl)phenyl)carbamate

[0500]

[0501]A mixture of 3-aminobenzyl alcohol (1.365 g, 11.08 mmol) in dry tetrahydrofuran (15 mL) was treated at 23° C. with di-tert-butyl dicarbonate (2.53 g, 11.59 mmol) and the resulting mixture was stirred for 72 hours (the mixture became homogeneous after 5 min). The reaction mixture was then concentrated under reduced pressure and the oily residue was chromatography on silica gel (elution toluene-ethyl acetate 8:2) to give 2.48 g (100% yield) of the title material as a thick syrup which crystallized to a white solid in the fridge. HPLC (Method A): 1.715 min. 1H NMR (CDCl3, 400 MHz) δ ppm: 7.43 (br. s, 1H), 7.26 (t, J=7.9 Hz, 1H), 7.20 (br. d, J=8.0 Hz, 1H), 7.02 (br. d, J=7.5 Hz, 1H), 6.49 (br. s, 1H), 4.65 (d, J=6.0 Hz, 2H), 1.76 (t, J=6.0 Hz, 1H), 1.51 (s, 9H).

tert-Butyl (3-(((6-methoxy-2-(2-methoxyimidazo...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
pHaaaaaaaaaa
temperatureaaaaaaaaaa
wavelengthaaaaaaaaaa
Login to View More

Abstract

The present invention provides imidazopyridazine compounds or imidazothiadiazole compounds of Formula I having the structure: (I) wherein X1, X2, X3, X4, X5, Y, W, R1, R2, R3, R4, R5 and (II) are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application is the National Stage of International Application No. PCT / CA2016 / 000050, filed on Feb. 25, 2016, which claims the benefit of priority from U.S. Provisional Patent Application No. 62 / 120,971, filed on Feb. 26, 2015, the contents of which are incorporated by reference herein in their entirety.FIELD OF THE INVENTION[0002]The present invention provides novel imidazopyridazine and imidazothiadiazole inhibitors of platelet aggregation which are useful in preventing or treating thromboembolic disorders. This invention also relates to pharmaceutical compositions containing these compounds and methods of using the same.BACKGROUND OF THE INVENTION[0003]Thromboembolic diseases remain the leading cause of death in developed countries despite the availability of anticoagulants such as warfarin (COUMADIN®), heparin, low molecular weight heparins (LMWH), synthetic pentasaccharides, and antiplatelet agents such as aspirin and clopidogrel...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(United States)
IPC IPC(8): C07D513/04A61K31/433A61P9/00A61K31/4439A61K31/497A61K31/501A61K31/506
CPCC07D513/04A61K31/433A61K31/4439A61K31/497A61K31/501A61K31/506A61P9/00C07B2200/07C07B2200/09
Inventor BANVILLE, JACQUES
Owner UNIV DE MONTREAL
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com